1. Field
This invention relates to resolving ischemia by inducing formation of blood vessels through therapeutic angiogenesis.
2. Relevant Art
A major component of morbidity and mortality attributable to cardiovascular disease occurs as a consequence of the partial or complete blockage of vessels carrying blood in the coronary and/or peripheral vasculature. When such vessels are partially occluded, lack of blood flow causes ischemia to the muscle tissues supplied by such vessel, consequently inhibiting muscle contraction and proper function. Total occlusion of blood flow causes necrosis of the muscle tissue.
Blood vessel occlusions are commonly treated by mechanically enhancing blood flow in the affected vessels. Such mechanical enhancements are often provided by employing surgical techniques that attach natural or synthetic conduits proximal and distal to the areas of occlusion, thereby providing bypass grafts, or revascularization by various means to physically enlarge the vascular lumen at the site of occlusion. These revascularization procedures involve such devices as balloons, endovascular knives (atherectomy), and endovascular drills. The surgical approach is accompanied by significant morbidity and even mortality, while the angioplasty-type processes are complicated by recurrent stenoses in many cases.
In some individuals, blood vessel occlusion is partially compensated by natural processes, in which new vessels are formed (termed xe2x80x9cangiogenesisxe2x80x9d) and small vessels are enlarged (termed xe2x80x9carteriogenesisxe2x80x9d) to replace the function of the impaired vessels. These new conduits may facilitate restoration of blood flow to the deprived tissue, thereby constituting xe2x80x9cnatural bypassesxe2x80x9d around the occluded vessels. However, some individuals are unable to generate sufficient collateral vessels to adequately compensate for the diminished blood flow caused by cardiovascular disease. Accordingly, it would be desirable to provide a method and apparatus for delivering agents to help stimulate the natural process of therapeutic angiogenesis to compensate for blood loss due to an occlusion in a coronary and peripheral arteries in order to treat ischemia.
A method is disclosed. In one embodiment the method includes positioning a delivery device such as a catheter at a location in a blood vessel and advancing the delivery device a distance into a wall of the blood vessel to a treatment site. A treatment agent is then introduced through the delivery device to the treatment site. The method also includes identifying a treatment site based on imaging a thickness of a portion of the wall of the blood vessel. In the example of introducing a treatment agent that would stimulate a therapeutic angiogenesis response, the method describes a technique for accurately delivering a treatment agent into the wall of the blood vessel or beyond the wall of the blood vessel as the particular situation may dictate. The method utilizes imaging of a thickness of the wall of a blood vessel to accurately place the treatment agent. Suitable imaging techniques include, but are not limited to, ultrasonic imaging, optical imaging, and magnetic resonance imaging.
In another embodiment, a method includes introducing a treatment agent in a sustained release composition or carrier. Treatment agents that can sustain their effectiveness for a period of up to one to ten weeks, preferably two to eight weeks, offer maximum benefit for the stimulation of therapeutic angiogenesis. Methods of inducing coronary or peripheral therapeutic angiogenesis by local delivery of sustained release treatment agents using percutaneous devices are described. Such devices may be intraventricular (coronary) or intravascular (coronary and peripheral).
In another embodiment, a method includes placing a treatment agent in or around a blood vessel or other tissue that stimulates therapeutic angiogenesis by inducing an inflammation response in tissue.
In still another embodiment, a sustained-release composition comprising a treatment agent in a form suitable for transvascular delivery is described. Also, a composition comprising a carrier including a treatment agent and an opsonin-inhibitor coupled to the carrier.
In a further embodiment, an apparatus is described that allows the accurate introduction of a treatment agent in or around a blood vessel. The apparatus includes, for example, a catheter body capable of traversing a blood vessel and a dilatable balloon assembly coupled to the catheter body comprising a balloon having a proximal wall. A needle body is disposed within the catheter body and comprises a lumen having dimensions suitable for a needle to be advanced there through. The needle body includes an end coupled to the proximal wall of the balloon. The apparatus also includes an imaging body disposed within the catheter body and comprising a lumen having a dimension suitable for a portion of an imaging device to be advanced there through. The apparatus further includes a portion of an imaging device disposed within the imaging body adapted to generate imaging signals of the blood vessel, including imaging signals of a thickness of the wall of a blood vessel. An apparatus such as described is suitable for accurately introducing a treatment agent at a desired treatment site in or around a blood vessel.